Aging impairs flow-induced dilation in coronary arterioles: role of NO and H2O2

作者：Kang Lori S; Reyes Rafael A; Muller Delp Judy M^*

来源：American Journal of Physiology - Heart and Circulatory Physiology, 2009, 297(3): H1087-H1095.

DOI：10.1152/ajpheart.00356.2009

• reactive oxygen species
• superoxide dismutase
• hydroxyl radical
• deferoxamine
• nitric oxide
• hydrogen peroxide

Kang LS, Reyes RA, Muller-Delp JM. Aging impairs flow-induced dilation in coronary arterioles: role of NO and H2O2. Am J Physiol Heart Circ Physiol 297: H1087-H1095, 2009. First published July 17, 2009; doi: 10.1152/ajpheart.00356.2009.-Aging contributes significantly to the development of cardiovascular disease and is associated with elevated production of reactive oxygen species (ROS). The beneficial effects of nitric oxide (NO)-mediated vasodilation are quickly abolished in the presence of ROS, and this effect may be augmented with aging. We previously demonstrated an age-induced impairment of flow-induced dilation in rat coronary arterioles. Therefore, the purpose of this study was to determine the effects of O-2(-) scavenging, as well as removal of H2O2, the byproduct of O-2(-) scavenging, on flow-mediated dilation in coronary resistance arterioles of young (4 mo) and old (24 mo) male Fischer 344 rats. Flow increased NO and H2O2 production as evidenced by enhanced diaminofluorescein and dichlorodihydrofluorescein fluorescence, respectively, whereas aging reduced flow-induced NO and H2O2 production. Endothelium-dependent vasodilation was evaluated by increasing intraluminal flow (5-60 nl/s) before and after treatment with the superoxide dismutase mimetic Tempol (100 mu M), the H2O2 scavenger catalase (100 U/ml), or Tempol plus catalase. Catalase reduced flow-induced dilation in both groups, whereas Tempol and Tempol plus catalase diminished vasodilation in young but not old rats. Tempol plus deferoxamine (100 mu M), an inhibitor of hydroxyl radical formation, reversed Tempol-mediated impairment of flow-induced vasodilation in young rats and improved flow-induced vasodilation in old rats compared with control. Immunoblot analysis revealed increases in endogenous superoxide dismutase, catalase, and nitrotyrosine protein levels with aging. Collectively, these data indicate that NO- and H2O2-mediated flow-induced signaling decline with age in coronary arterioles and that elevated hydroxyl radical formation contributes to the age-related impairment of flow-induced vasodilation.

• 出版日期2009-9